Download The Analgesic Efficacy of Celecoxib, Pregabalin, and Their

Pain Medicine
Section Editor: Spencer S. Liu
The Analgesic Efficacy of Celecoxib, Pregabalin, and
Their Combination for Spinal Fusion Surgery
Scott S. Reuben, MD*
Asokumar Buvanendran, MD†
Jeffrey S. Kroin, PhD†
Karthik Raghunathan, MD*
BACKGROUND: As optimal pain relief after surgery is difficult to achieve with the use
of just one drug, many pain experts advocate the use of two or more classes of
medications so as to reduce the side effects from any one drug. In this trial, we
assessed the analgesic efficacy of administering perioperative celecoxib, pregabalin, or both after spinal fusion surgery.
METHODS: Eighty patients scheduled to undergo elective decompressive lumbar
laminectomy with posterior spinal fusion were randomized to receive oral medications: placebo 1 h before and 12 h after surgery, celecoxib 400 mg 1 h before and
celecoxib 200 mg 12 h after surgery, pregabalin 150 mg 1 h before and 12 h after
surgery, or a pregabalin/celecoxib combination of 400 mg/150 mg 1 h before and
200 mg/150 mg 12 h after surgery.
RESULTS: The pregabalin/celecoxib group consumed the least patient-controlled
morphine. Celecoxib alone or pregabalin alone also reduced opioid use compared
with placebo, but not as much as when combined. The pregabalin/celecoxib
combination was the most effective treatment for reducing pain both at rest and
with movement over the 24-h postoperative time period. Hemodynamics and
respiratory rate did not differ among the four treatment groups. Fewer patients
experienced nausea in the pregabalin/celecoxib group compared with that in the
placebo group.
CONCLUSION: The perioperative administration of the combination of celecoxib and
pregabalin improved analgesia and caused fewer side effects, than either analgesic
drug alone after spinal fusion surgery.
(Anesth Analg 2006;103:1271–7)
D
espite major improvements in our understanding
of acute pain physiology over the past decade, approximately 80% of patients undergoing surgical procedures
experience postoperative pain (1). Acute postoperative
pain is a predictor of chronic pain syndromes as a result
of surgery (2). Although opioids are an important component of postoperative pain management, they are
associated with side effects (3), and so, the multimodal
analgesic approach has been recommended for the management of acute postoperative pain (4,5).
Cyclooxygenase (COX)-2 specific nonsteroidal antiinflammatory drugs (NSAIDs) and ␣2-␦ subunit calcium channel ligands (gabapentin and pregabalin) are
two mechanistically different types of analgesics that
have demonstrated efficacy after a variety of surgical
From the *Department of Anesthesiology, Baystate Medical
Center, Springfield, Massachusetts; and †Department of Anesthesiology, Rush Medical College, Chicago, Illinois.
Accepted for publication June 20, 2006.
Presented in part at the International Anesthesia Research
Society 80th Clinical and Scientific Congress, March 20, 2006, San
Francisco, CA.
Address correspondence and reprint requests to Dr. Reuben, Department of Anesthesiology, Baystate Medical Center, 759 Chestnut St.,
Springfield, MA 01199. Address e-mail to [email protected].
Copyright © 2006 International Anesthesia Research Society
DOI: 10.1213/01.ane.0000237279.08847.2d
Vol. 103, No. 5, November 2006
procedures (6,7). Gabapentin can enhance the analgesic effect of morphine in both animal models (8) and
volunteers (9). Both ␣2-␦ ligands and NSAIDs can
interact synergistically or additively to reverse hyperalgesia associated with peripheral inflammation (10).
The combination of gabapentin and rofecoxib, a
COX-2 selective NSAID, was shown to be superior to
either single drug alone for postoperative pain management (7). Recently, both celecoxib (11,12) and gabapentin (13) have been demonstrated to have analgesic
efficacy after spinal fusion surgery.
Although structurally similar to gabapentin, pregabalin has greater analgesic efficacy in rodent models
of neuropathic pain (14,15), and exhibits linear pharmacokinetics across its therapeutic dose range with
low intersubject variability (14,15). No study has
evaluated the efficacy of administering pregabalin
with or without a NSAID for postsurgical analgesia.
The hypothesis of this prospective, double-blind, randomized, placebo-controlled trial is that after spinal
fusion surgery, a combination of celecoxib and pregabalin will demonstrate superior analgesic efficacy than
either drug alone and cause fewer side effects.
METHODS
Patients
After IRB approval, written informed consent was
obtained between July 2004 and October 2005 from
1271
patients scheduled to undergo elective decompressive
lumbar laminectomy with instrumented posterior spinal fusion. Patients were eligible for participation if
they were at least 18 years old, weighed more than 40
kg, and could operate a patient-controlled analgesia
(PCA) device after presurgery instructions. Exclusion
criteria included known allergy, sensitivity, or contraindications to sulfa, morphine, or any NSAID; renal insufficiency; a history of peptic ulcer; a history of alcohol or
substance abuse; ongoing therapy with sustained-release
opioids; seizure disorder; and pregnancy.
Study Design
Study medications were celecoxib 200 mg capsules,
pregabalin 150 mg capsules, and placebo capsules that
matched the celecoxib or pregabalin capsules in color
and size. Patients were assigned to one of four treatment groups in a parallel double-blind randomized
manner:
1. The placebo group received placebo capsules (2)
1 h before the anesthetic induction and 12 h after
surgery (identically matched to study drugs).
2. The celecoxib group received celecoxib 400 mg
and a placebo capsule 1 h before the anesthetic
induction and celecoxib 200 mg and placebo
capsules, 12 h after surgery.
3. The pregabalin group received pregabalin 150
mg and placebo capsules 1 h before the anesthetic induction and pregabalin 150 mg and
placebo capsules, 12 h after surgery.
4. The pregabalin/celecoxib group received celecoxib 400 mg and pregabalin 150 mg 1 h before
the anesthetic induction and celecoxib 200 mg
and pregabalin 150 mg 12 h after surgery.
Before the start of the study, a medical center
pharmacist prepared an allocation protocol which
randomized these four drug treatments among 100
patients. Each new patient was assigned a consecutive
study number. The study medications were administered at the medical center on the day of surgery by a
nurse. The celecoxib dose of 400 mg 1 h before
anesthetic induction and 200 mg 12 h after surgery
was based on a previous study in which these doses
and daily timing were administered after spinal fusion
surgery (11). The pregabalin dose of 150 mg 1 h before
anesthetic induction and 150 g 12 h after surgery was
based on the product information sheet that recommends a maximum dose of 300 mg/day for pain
syndromes (14,15).
Spinal fusion was performed at either one or two
levels from L4 to S1 using similar carbon fiber cages
with pedicle screw and plate instrumentation. All
procedures were performed by use of a partialthickness, posterior iliac-crest bone graft harvested
through a lateral oblique incision just cephalad to the
crest. Before surgery, both the laminectomy and iliaccrest harvest incision sites were infiltrated with 10 mL
bupivacaine 0.25%.
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Celecoxib and Pregabalin for Postoperative Pain
Anesthesia was induced with propofol (2 mg/kg),
morphine 0.3 mg/kg, and maintained with isoflurane
70% N2O in O2. Patients were connected to a PCA
pump (Abbott PCA Plus, Abbott Park, Chicago, IL) on
arrival in the postanesthesia care unit. Initial settings
were as follows: incremental dose, 2 mg; lockout
interval, 8 min; and 4-h limit, 40 mg. The incremental
dose was increased to 2.5 mg, and the 4-h limit was
increased to 50 mg if analgesia was inadequate after
1 h. If analgesia remained inadequate after an additional hour, the incremental dose was further increased to 3.0 mg, and the 4-h limit was increased to
60 mg.
No other analgesic supplement was given. However, any patient with severe pain that was not
adequately controlled by PCA morphine could, by
agreement with the principal investigator, be withdrawn from the study so that alternative analgesic
dosing could be offered. Any patient in this category
would not be replaced with a newly enrolled patient.
Outcomes
Outcome measures for the study were assessed by
a research or acute pain service nurse who was
blinded to patients’ group assignments. Patients were
asked to quantify their pain on a verbal rating scale
between 0 and 10, with 0 representing no pain and 10
the worst imaginable pain. Pain assessments were
made both at rest and with movement. Pain with
movement was recorded after the patient completed a
90° logroll while in bed.
Intraoperative blood loss was determined by combining the blood collected in the suction canister as
well as by estimating the blood present in the surgical
sponges.
Sedation scores were measured on a numerical
score of 1–5 (1, completely awake; 2, awake but
drowsy; 3, asleep but responsive to verbal commands;
4, asleep but responsive to tactile stimulus; 5, asleep
and not responsive to any stimulus).
Pain scores, sedation scores, heart rate, oxygen
saturation (SpO2), mean arterial blood pressure, respiratory rate, and morphine use were recorded by a
study nurse 1 h after arrival in the postanesthesia care
unit and subsequently at 4, 8, 12, 16, 20, and 24 h. Bed
rest was enforced for the first 24 h postoperatively.
The incidences of respiratory depression (respiratory
rate ⬍ 8 breaths/min or SpO2 ⬍ 90% without oxygen
supplementation) and hypotension (mean arterial
blood pressure ⬍ 80% of baseline) were recorded.
Other symptoms were assessed, including nausea,
vomiting, constipation, difficulty passing urine, difficulty concentrating, drowsiness or difficulty staying
awake, feeling light-headed or dizzy, feeling confused, feelings of general fatigue or weakness, itchiness, dry mouth, and headache.
ANESTHESIA & ANALGESIA
Table 1. Patient Demographics and Surgical Data
Pregabalin
Pregabalin/
Celecoxib
Treatment group
Placebo
Celecoxib
Number
Gender (M/F)
Age (yr)
Weight (kg)
Height (cm)
Duration of surgery (min)
Spinal levels fused
1 level
2 levels
Blood loss (mL)
20
13/7
43 ⫾ 14
79 ⫾ 17
169 ⫾ 14
181 ⫾ 29
20
12/8
46 ⫾ 18
83 ⫾ 17
172 ⫾ 17
188 ⫾ 34
20
13/7
42 ⫾ 12
82 ⫾ 15
172 ⫾ 15
186 ⫾ 27
20
11/9
44 ⫾ 16
84 ⫾ 17
171 ⫾ 19
190 ⫾ 36
12
8
395 ⫾ 55
11
9
388 ⫾ 62
10
10
410 ⫾ 75
11
9
403 ⫾ 65
Data are presented as mean ⫾ SD.
There were no statistical differences among groups.
Statistical Analysis
Sample size was estimated by analyzing previous
data from studies comparing verbal rating-scale pain
scores between patients receiving a COX-2 selective
inhibitor and those receiving placebo after spinal
fusion surgery (11,12). With 90% power, a mean
difference of 2.9, a standard deviation of 1.0, and ␣ ⫽
0.05, a power analysis of ANOVA testing on four
independent means would require 16 patients per
group. To be conservative, we planned to initially
enroll 20 patients per group. At the end of the study,
if there was a drop-out in any group due to a protocol
violation, new patients would be enrolled and randomly assigned to treatment groups to increase the
total to 20 per group. Morphine consumption, pain at
rest, pain with movement, heart rate, mean arterial
blood pressure, and respiratory rate were compared
among the four groups over the postoperative time
points, with repeated measures linear fixed model. If
group differences were significant (P ⬍ 0.05), then
treatment groups were compared at each time point
with Tukey-Kramer post hoc testing. Sedation scores
were compared among the four groups by repeated
measures analysis of variance for assessment of time
and treatment effects. If differences were found, a
Bonferroni post hoc test was performed. Total PCA
morphine use, duration of surgery, and intraoperative
blood loss were compared among the four groups
with ANOVA, and Tukey-B post hoc testing. Demographic data were analyzed using ANOVA or ␹2 test,
as appropriate. The incidence of each side effect was
compared with an omnibus ␹2 test, and if significant
(P ⬍ 0.05), pairwise post hoc comparisons of each of the
three drug groups to the placebo group were made
with Fisher’s exact test (P ⬍ 0.0167 for significance).
RESULTS
Patients
The clinical trial was conducted between July 2004
and October 2005. Seven patients were withdrawn
from the study due to protocol violation: two patients
had more than two levels of fusion, two patients used
cadaver rather than autogenous iliac crest graft, and
Vol. 103, No. 5, November 2006
three patients were not administered their study
drugs according to protocol. These subjects were
replaced by new study patients to make the number of
patients in each group ⫽ 20. No patient was withdrawn from the study because of severe pain requiring additional analgesic beyond the PCA protocol.
Table 1 lists the characteristics of the 80 patients
completing the clinical trial. There were no differences
in demographic characteristics, surgical duration, or
number of spinal levels fused.
Morphine Consumption
Figure 1 shows the average PCA-administered
drug consumption at each of the postoperative time
intervals up to 24 h. Repeated measure analysis demonstrated a difference among the four treatment
groups (F ⫽ 283.3, P ⬍ 0.001), and also a group by time
interaction (F ⫽ 17.83, P ⬍ 0.001). Post hoc analysis
showed that the pregabalin/celecoxib group required
the least amount of opioid. Celecoxib alone or pregabalin alone also reduced morphine consumption
Figure 1. Morphine delivered by patient-controlled analgesia
(PCA) after arrival in the postanesthesia care unit (PACU).
The group receiving perioperative pregabalin/celecoxib
consumed the least amount of morphine over this 24-h
postoperative period. Data are shown as mean ⫾ sem;
*different from placebo (P ⬍ 0.01); †different from celecoxib
(P ⬍ 0.01); ‡different from pregabalin (P ⬍ 0.01); §different
from pregabalin/celecoxib combination (P ⬍ 0.01).
© 2006 International Anesthesia Research Society
1273
treatment group consistently reduced pain intensity at
rest throughout the postoperative period. With movement, pain scores differed by group (F ⫽ 69.6, P ⬍ 0.001),
and group by time (F ⫽ 2.25, P ⫽ 0.003). Post hoc testing
demonstrated that the pregabalin/celecoxib combination was the most effective treatment for reducing pain
with movement.
Side Effects
Figure 2. Verbal rating scale (VRS) pain at rest over the 24-h
postoperative period after arrival at the postanesthesia care
unit (PACU). The group receiving perioperative
pregabalin/celecoxib experienced the least amount of pain.
Data are shown as mean ⫾ sem; *different from placebo (P ⬍
0.05); †different from celecoxib (P ⬍ 0.05); §different from
pregabalin/celecoxib combination (P ⬍ 0.05).
compared with placebo, but not as much as when
combined. Total 24-h cumulative morphine consumption was different among the four treatment groups
(F ⫽ 269.1, P ⬍ 0.001), with each group statistically
different from each other: placebo 134.0 ⫾ 3.3 mg,
celecoxib 88.0 ⫾ 2.4 mg, pregabalin 77.4 ⫾ 1.7 mg,
pregabalin/celecoxib 43.0 ⫾ 1.3 mg (mean ⫾ sem).
Pain Scores
Figures 2 and 3 display postoperative pain scores
over time both at rest and with movement. At rest,
pain scores differed among the four groups (F ⫽ 28.9,
P ⬍ 0.001), and also group by time (F ⫽ 5.64, P ⬍ 0.001).
Post hoc testing showed that the pregabalin/celecoxib
Figure 3. Verbal rating scale (VRS) pain with movement over
the 24-h postoperative period after arrival at the postanesthesia
care unit (PACU). The group receiving perioperative
pregabalin/celecoxib experienced the least amount of pain.
Data are shown as mean ⫾ sem; *different from placebo (P ⬍
0.05); †different from celecoxib (P ⬍ 0.05); ‡different from
pregabalin (P ⬍ 0.05); §different from pregabalin/celecoxib
combination (P ⬍ 0.05).
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Celecoxib and Pregabalin for Postoperative Pain
Hemodynamics and respiratory rate did not differ
among the four treatment groups during the postoperative period (Table 2). The level of sedation during
the postoperative period was less in the celecoxib
group and the pregabalin/celecoxib group when compared with that in the placebo or pregabalin group
(Table 3). The overall incidence of side effects is
summarized in Table 4. Fewer patients experienced
nausea in the pregabalin/celecoxib group compared
with that in the placebo group. Drowsiness was less
frequent with pregabalin/celecoxib or celecoxib alone
than placebo. There were fewer occurrences of excessive sedation in the pregabalin/celecoxib group than
in the placebo group.
DISCUSSION
This study revealed that the perioperative administration of the combination of celecoxib and pregabalin resulted in improved analgesia compared with
either analgesic drug alone after spinal fusion surgery.
This combination produced a significant reduction in
pain scores and in morphine use during the first 24
postoperative hours. The pregabalin/celecoxib combination was the only treatment that significantly reduced the incidence of nausea and excess sedation.
Pregabalin has demonstrated analgesic efficacy for
neuropathic pain (14,15), fibromyalgia syndrome (16),
and in a postdental pain model (17). Biochemical
studies have identified the ␣2-␦ (Type 1) receptor as
the primary binding site for both gabapentin and
pregabalin (18,19). Binding of pregabalin to the ␣2-␦
subunit of voltage-gated calcium channels alters the
kinetics and voltage dependence of calcium currents
(20). By reducing calcium influx at nerve terminals,
pregabalin reduces the release of several neurotransmitters, including glutamate, noradrenaline, calcitonin
gene-related peptide, and substance P (21–23). This
reduction in neurotransmitter release is presumed to
account for pregabalin’s analgesic actions. As demonstrated in the present study, pregabalin had no effect
on arterial blood pressure or heart rate, which is
consistent with animal experiments showing that intrathecal administration of the related compound
gabapentin does not alter resting or acutely evoked
autonomic outflow (24).
Although parenteral opioids are still considered the
foundation for the treatment of moderate to severe
pain (25), sufficient analgesia cannot be achieved
without the risk of significant adverse events (26). The
ANESTHESIA & ANALGESIA
Table 2. Postoperative Heart Rate, Mean Arterial Blood Pressure, and Respiratory Rate
Hours after
surgery
Preoperative
HR (bpm)
MAP (mm Hg)
RR (breaths/min)
1h
HR (bpm)
MAP (mm Hg)
RR (breaths/min)
4h
HR (bpm)
MAP (mm Hg)
RR (breaths/min)
8h
HR (bpm)
MAP (mm Hg)
RR (breaths/min)
12 h
HR (bpm)
MAP (mm Hg)
RR (breaths/min)
16 h
HR (bpm)
MAP (mm Hg)
RR (breaths/min)
20 h
HR (bpm)
MAP (mm Hg)
RR (breaths/min)
24 h
HR (bpm)
MAP (mm Hg)
RR (breaths/min)
Placebo
(n ⫽
20)
Celecoxib
(n ⫽ 20)
85 ⫾ 16
110 ⫾ 25
15 ⫾ 5
81 ⫾ 13
107 ⫾ 21
16 ⫾ 6
78 ⫾ 21
113 ⫾ 23
16 ⫾ 4
79 ⫾ 17
111 ⫾ 21
15 ⫾ 5
88 ⫾ 19
107 ⫾ 23
14 ⫾ 4
84 ⫾ 15
105 ⫾ 25
15 ⫾ 3
79 ⫾ 23
110 ⫾ 21
13 ⫾ 2
81 ⫾ 21
108 ⫾ 23
15 ⫾ 3
85 ⫾ 17
110 ⫾ 21
12 ⫾ 3
81 ⫾ 13
105 ⫾ 21
14 ⫾ 3
77 ⫾ 22
112 ⫾ 23
15 ⫾ 3
78 ⫾ 19
107 ⫾ 21
15 ⫾ 2
84 ⫾ 18
111 ⫾ 21
11 ⫾ 3
82 ⫾ 13
108 ⫾ 23
14 ⫾ 3
77 ⫾ 21
113 ⫾ 22
16 ⫾ 3
80 ⫾ 19
109 ⫾ 21
15 ⫾ 4
84 ⫾ 16
109 ⫾ 23
12 ⫾ 2
83 ⫾ 14
110 ⫾ 21
15 ⫾ 3
78 ⫾ 23
111 ⫾ 24
14 ⫾ 2
79 ⫾ 17
110 ⫾ 19
14 ⫾ 2
81 ⫾ 16
108 ⫾ 19
11 ⫾ 2
79 ⫾ 15
107 ⫾ 21
14 ⫾ 3
78 ⫾ 21
111 ⫾ 20
14 ⫾ 3
79 ⫾ 18
107 ⫾ 18
13 ⫾ 4
80 ⫾ 13
89 ⫾ 11
10 ⫾ 2
81 ⫾ 11
89 ⫾ 13
13 ⫾ 2
78 ⫾ 16
90 ⫾ 14
13 ⫾ 2
78 ⫾ 14
91 ⫾ 15
14 ⫾ 3
81 ⫾ 14
88 ⫾ 11
10 ⫾ 3
78 ⫾ 12
89 ⫾ 11
13 ⫾ 3
79 ⫾ 11
87 ⫾ 12
14 ⫾ 1
80 ⫾ 13
86 ⫾ 14
13 ⫾ 1
Pregabalin
(n ⫽ 20)
Pregabalin/
Celecoxib
(n ⫽ 20)
Data are presented as mean ⫾ SD.
HR ⫽ heart rate; MAP ⫽ mean arterial blood pressure; RR ⫽ respiratory rate.
There were no statistical differences among the four groups.
opioid doses necessary for complete relief of spontaneous pain at rest (tonic pain) have no effect on
movement-associated (phasic) pain (27,28). Both COX-2
NSAIDs (29) and ␣2-␦ ligands (6) have been demonstrated to have analgesic efficacy during pain at rest
and with movement. Although both analgesics alone
are capable of reducing postoperative opioid use by
20 –50%, it remains to be determined whether this can
result in a significant reduction in opioid-related adverse events, thereby accelerating the rehabilitation
process and reducing postoperative morbidity (30).
Only one clinical study evaluating the perioperative
analgesic effect of gabapentin (13) demonstrated a
reduction in opioid-related side effects (vomiting and
urinary retention). Meta-analysis studies of NSAIDs
and COX-2 inhibitors highlight the importance of
Table 3. Postoperative Sedation Scores
Time period
(h)
Placebo
(n ⫽ 20)
Celecoxib
(n ⫽ 20)
1
4
8
12
16
20
24
3.3 ⫾ 0.5
3.4 ⫾ 0.7
3.2 ⫾ 0.6
3.4 ⫾ 1.1
3.3 ⫾ 0.9
3.4 ⫾ 0.9
3.5 ⫾ 0.7
3.1 ⫾ 0.7
2.4 ⫾ 0.8*
2.3 ⫾ 0.5*
2.4 ⫾ 0.6*
2.3 ⫾ 0.9*
2.4 ⫾ 0.8*
2.5 ⫾ 0.9*
Pregabalin
(n ⫽ 20)
3.2 ⫾ 0.9
3.3 ⫾ 0.6
3.1 ⫾ 0.7
3.4 ⫾ 0.7
3.4 ⫾ 1.1
3.3 ⫾ 0.5
3.4 ⫾ 0.8
Pregabalin/
Celecoxib
(n ⫽ 20)
3.0 ⫾ 0.7
2.3 ⫾ 0.7*
2.2 ⫾ 0.6*
2.3 ⫾ 0.7*
2.4 ⫾ 0.8*
2.3 ⫾ 0.7*
2.4 ⫾ 0.6*
Data are presented as mean ⫾ SD.
* P ⬍ 0.05 when compared with placebo and pregabalin.
Vol. 103, No. 5, November 2006
© 2006 International Anesthesia Research Society
1275
Table 4. Incidence of Side Effects
Side effect
Placebo
(n ⫽ 20)
Celecoxib
(n ⫽ 20)
Nausea
Vomiting
Constipation
Difficulty passing urine
Difficulty concentrating
Drowsiness
Feeling light-headed or dizzy
Feeling confused
Feeling of general fatigue
Itchiness
Dry mouth
Headache
Respiratory depression
Excessive sedation
Hypoxemia
Hypotension
10 (50)
7 (35)
2 (10)
4 (20)
5 (25)
10 (50)
6 (30)
3 (15)
5 (25)
4 (20)
5 (25)
5 (25)
3 (15)
7 (35)
6 (30)
0 (0)
5 (25)
4 (20)
1 (5)
2 (10)
3 (15)
2 (10)*
2 (10)
1 (5)
2 (10)
2 (10)
2 (10)
1 (5)
0 (0)
1 (5)
0 (0)
0 (0)
Pregabalin
(n ⫽ 20)
6 (30)
4 (20)
1 (5)
2 (10)
2 (10)
5 (25)
4 (25)
2 (10)
2 (10)
1 (10)
2 (10)
2 (10)
0 (0)
5 (25)
1 (5)
0 (0)
Pregabalin/
Celecoxib
(n ⫽ 20)
P
2 (10)*
1 (5)
2 (10)
0 (0)
1 (5)
2 (10)*
3 (15)
1 (5)
1 (5)
0 (0)
0 (0)
1 (5)
0 (0)
0 (0)*
0 (0)
0 (0)
0.046
0.131
0.868
0.217
0.297
0.008
0.412
0.632
0.249
0.140
0.094
0.146
0.025
0.007
0.001
NA
Data inside the parentheses are percentages.
Respiratory depression, ⱕ8 breaths/min.
Excessive sedation, sedation score ⱖ 4.
Hypoxemia, SpO2 ⬍ 90%.
Hypotension, mean arterial blood pressure ⬍ 80% of baseline.
P, ␹2 P value for full contingency table.
* Different from placebo (P ⬍ 0.0167).
using more than one nonopioid analgesic in the multimodal management of acute pain (31,32).
Without a full dose-response study and associated
ED50s, it is not possible to infer that the combination
of celecoxib and pregabalin has more than just an
additive effect. Another study with rofecoxib and
gabapentin perioperative administration for abdominal hysterectomy did not support synergy between a
COX-2 inhibitor and a ␣2-␦ ligand (7). Another limitation of our study is that preoperative narcotic usage
was not used as a covariant in analyzing postoperative
opioid requirements.
In summary, the present study demonstrates that the
perioperative administration of the pregabalin/celecoxib
combination reduces both postoperative pain and
opioid-related side effects more effectively than either
drug alone. These results from spinal fusion surgery
support the wider clinical use of this specific drug
combination in the postsurgical setting.
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